Lung cancer is a typical example of intractable cancers and is the first and second leading causes of cancer deaths in Japanese men and women, respectively, in 2009. The types of lung cancer are broadly classified into small cell cancer (small cell lung cancer) accounting for approximately 10% and non-small cell cancer accounting for approximately 90%. The types of non-small cell cancer are further classified into adenocarcinoma (lung adenocarcinoma) (60%), squamous cell carcinoma (lung squamous cell carcinoma) (25%), and large-cell cancer (large-cell lung cancer) (5%).
The small cell lung cancer is a very high-grade cancer and therefore has a strong tendency to metastasize even in an early stage. As seen in previous cases, it is likely that the small cell lung cancer has already metastasized systemically when found. Thus, non-surgical therapy is commonly selected for this cancer even if its metastasis to lymph nodes or other tissues is not confirmed. Since this cancer is highly sensitive to chemotherapy or radiation, chemotherapy is central to the non-surgical therapy.
By contrast, the non-small cell lung cancer, which constitutes a large portion of lung cancer cases, is low sensitive to chemotherapy or radiation. For its treatment, it is important to find the cancer relatively early and remove the lesion by surgical therapy.
Tests for lung cancer can be broadly classified, depending on the purposes of the tests, into three: (1) lung cancer assessment to test the probability of lung cancer; (2) definite diagnosis of lung cancer to confirm that this probable lung cancer is definitely lung cancer; and (3) determination of the stage of lung cancer progression to test the histological type and stage of progression of the definitely diagnosed lung cancer.
These tests generally adopt a method which involves detecting an abnormal shadow in the lung field by chest X-ray examination or CT scan and subsequently finally determining a cancer type and comprehensively determining the stage of progression by bronchoscopy or by the pathological diagnosis of biopsy samples obtained using biopsy or the like. However, cases with small cell cancer coexisting with non-small cell cancer or borderline cancers might be given different diagnostic outcomes among pathologists. Accurate definite diagnosis has not yet been established for lung cancer.
In recent years, tumor markers have been used in cancer prognosis or the like. The tumor markers refer to substances produced by cancer cells or substances produced by cells in response to cancer cells. The amounts of the tumor markers contained in serum reflect the amount or histological type of tumor. The tumor markers can therefore serve as an index for, for example, determining the presence or absence of cancer and as such, can be used in diagnostic aids, the prediction of a histological type or the stage of progression, the determination of therapeutic effects, the prediction of recurrence, prognosis, etc. Currently, some tumor markers, such as CEA, CYFRA, NSE, ProGRP, SCC, and SLX, are also known for lung cancer (Non Patent Literatures 1 to 3). All of these tumor markers, however, are based on the difference in protein expression level, i.e., increase or decrease in protein expression, in blood or tissue between healthy persons and lung cancer patients. These tumor markers are usually expressed even in normal cells and are thus low specific for lung cancer. Hence, the obtained results present the problem of low reliability or detection sensitivity. In addition, lung cancer markers useful in determining the histological type of detected lung cancer have not yet been found.